Specificity of endogenous substrates for types A and B monoamine oxidase in rat striatum.
Studies were designed to evaluate specificity of the transmitter amines serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA), as well as the trace amines p-tyramine (p-TA) and beta-phenylethylamine (PEA) for types A and B monoamine oxidase (MAO) in rat striatum. 5-HT was found to be a specific substrate for the type A enzyme. However, the specificity of PEA for the type B enzyme was found to be concentration-dependent. When low concentrations of PEA and 5-HT were used to measure type B and type A activities, respectively, both clorgyline and deprenyl were highly selective for the sensitive form of MAO in vivo. However, as the concentration of PEA was increased, the type B inhibitor deprenyl became less effective in preventing deamination of PEA. Conversely, the type A inhibitor clorgyline became more effective in this regard. Kinetic analysis following selective in vivo inhibition showed PEA deamination by both forms of MAO with a 13-fold greater affinity for the type B enzyme. In vivo dose-response curves obtained with the common substrates DA and p-TA showed approximately 20% deamination by the B enzyme. Kinetic values for DA and p-TA deamination in in vivo-treated tissue possessing only type A or type B MAO activity, revealed a 2.5-fold greater affinity for the type A enzyme. These studies show the importance of concentration on substrate specificity in striatal tissue. The results obtained characterize the common substrate properties of DA and p-TA as well as of PEA in rat striatum. In addition, the presence of regional specificity for 5-HT deamination by only type A MAO is demonstrated.
D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology*; D004298:Dopamine / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism; D051381:Rats; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013379:Substrate Specificity; D014439:Tyramine / Q000378:metabolism
D007527:Isoenzymes; D010627:Phenethylamines; D012642:Selegiline; C029261:phenethylamine; D012701:Serotonin; D008995:Monoamine Oxidase; D003010:Clorgyline; D004298:Dopamine; D014439:Tyramine